Korean J Lab Med.  2009 Dec;29(6):497-504. 10.3343/kjlm.2009.29.6.497.

Usefulness of Silica Clotting Time for Detection of Lupus Anticoagulants

• Lee HR
• Kim JE
• Ha SH
• Kim HK
• Park S
• Cho HI

• KMID: 1781601
• DOI: http://doi.org/10.3343/kjlm.2009.29.6.497

Abstract

BACKGROUND
The presence of lupus anticoagulants (LA) is a strong risk factor for thrombosis in antiphospholipid syndrome. We investigated the usefulness of addition of silica clotting time (SCT) to the pre-existing dilute Russell's viper venom test (dRVVT) for detection of LA. Also, we analyzed differences in the thrombotic features and the characteristics of antiphospholipid antibodies between dRVVT and SCT. METHODS: A total of 167 patients positive for LA or anti-cardiolipin (anti-CL) antibody and 76 healthy controls were enrolled. The dRVVT and SCT were used for detection of LA. Anti-CL, anti-beta2-glycoprotein I (anti-beta2 GPI) and anti-prothrombin (anti-PT) antibodies were measured using commercial ELISA kits. RESULTS: In detection of thrombosis, the sensitivity of the combined test of SCT and dRVVT was 56.4%, which was higher than that of dRVVT alone (46.2%) or SCT alone (23.1%). The specificity of the combined test (80.9%) was comparable to that of dRVVT (81.9%). Also, odds ratio for predicting thrombosis was higher in the combined test than in dRVVT or SCT alone. When normalized LA ratio of the two tests was compared, the group of patients with higher ratio of SCT showed significantly higher prevalence of recurrent abortion and higher positivity of IgG types of anti-CL, anti-beta2 GPI and anti-PT than the group with higher ratio of dRVVT. CONCLUSIONS: Addition of SCT to dRVVT can improve the detection sensitivity of thrombosis in LA test. And the high normalized LA ratio of SCT may be a useful parameter for detection of recurrent abortion.

Keyword

Dilute Russell's viper venom test (dRVVT); Silica clotting time (SCT); Antiphospholipid antibody; Antiphospholipid syndrome; Vascular thrombosis; Pregnancy morbidity

MeSH Terms

Adult
Aged
Antibodies, Anticardiolipin/analysis
Antibodies, Antiphospholipid/analysis
Blood Coagulation Tests/*methods
Female
Humans
Immunoglobulin G/analysis
Immunoglobulin M/analysis
Lupus Coagulation Inhibitor/*blood
Male
Middle Aged
Prothrombin/immunology
Prothrombin Time/methods
Reagent Kits, Diagnostic
Sensitivity and Specificity
Silicon Dioxide/*chemistry
Thrombosis/diagnosis
beta 2-Glycoprotein I/immunology

Figure

• 

  Fig. 1. Comparison of IgG values of anti-CL (A), anti-β2 GPI (B) and anti-PT (C) in patients with lupus anticoagulant classified according to detection methods of lupus anticoagulant. The mean levels of anti-CL and anti-β2 GPI show significantly higher values in SCT group than in dRVVT group (P=0.016 and P=0.043, respectively). Box and whisker graphs shows median, 25th and 75th percentiles, range and outliers (circles and asterisks) of IgG values. Abbreviations: See Table 4.

Reference

1.McNeil HP., Chesterman CN., Krilis SA. Immunology and clinical importance of antiphospholipid antibodies. Adv Immunol. 1991. 49:193–280.

2.Alarcon-Segovia D., Deleze M., Oria CV., Sanchez-Guerrero J., Gomez-Pacheco L., Cabiedes J, et al. Antiphospholipid antibodies and the antiphospholipid syndrome in systemic lupus erythematosus. A prospective analysis of 500 consecutive patients. Medicine (Baltimore). 1989. 68:353–65.

3.Roubey RA. Autoantibodies to phospholipid-binding plasma proteins: a new view of lupus anticoagulants and other “antiphospholipid” autoantibodies. Blood. 1994. 84:2854–67.

4.de Laat B., Mertens K., de Groot PG. Mechanisms of disease: antiphospholipid antibodies-from clinical association to pathologic mechanism. Nat Clin Pract Rheumatol. 2008. 4:192–9.

5.Amoroso A., Mitterhofer AP., Del Porto F., Garzia P., Ferri GM., Galluzzo S, et al. Antibodies to anionic phospholipids and anti-beta2-GPI: association with thrombosis and thrombocytopenia in systemic lupus erythematosus. Hum Immunol. 2003. 64:265–73.

6.Galli M., Luciani D., Bertolini G., Barbui T. Lupus anticoagulants are stronger risk factors for thrombosis than anticardiolipin antibodies in the antiphospholipid syndrome: a systematic review of the literature. Blood. 2003. 101:1827–32.

7.Galli M., Luciani D., Bertolini G., Barbui T. Anti-beta 2-glycoprotein I, antiprothrombin antibodies, and the risk of thrombosis in the anti-phospholipid syndrome. Blood. 2003. 102:2717–23.

8.Miyakis S., Lockshin MD., Atsumi T., Branch DW., Brey RL., Cervera R, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006. 4:295–306.

9.Wisloff F., Jacobsen EM., Liestol S. Laboratory diagnosis of the antiphospholipid syndrome. Thromb Res. 2002. 108:263–71.

10.Derksen RH., de Groot PG. Tests for lupus anticoagulant revisited. Thromb Res. 2004. 114:521–6.

11.Galli M., Dlott J., Norbis F., Ruggeri L., Cler L., Triplett DA, et al. Lupus anticoagulants and thrombosis: clinical association of different coagulation and immunologic tests. Thromb Haemost. 2000. 84:1012–6.

12.Bevers EM., Galli M., Barbui T., Comfurius P., Zwaal RF. Lupus anticoagulant IgG's (LA) are not directed to phospholipids only, but to a complex of lipid-bound human prothrombin. Thromb Haemost. 1991. 66:629–32.

13.Ebeling F., Pettersson T., Muukkonen L., Vahtera E., Rasi V. Beta-2-glycoprotein I antibodies in patients with thrombosis. Scand J Clin Lab Invest. 2003. 63:111–8.

14.Forastiero RR., Martinuzzo ME., Cerrato GS., Kordich LC., Carreras LO. Relationship of anti beta2-glycoprotein I and anti prothrombin antibodies to thrombosis and pregnancy loss in patients with antiphospholipid antibodies. Thromb Haemost. 1997. 78:1008–14.

15.Oosting JD., Derksen RH., Bobbink IW., Hackeng TM., Bouma BN., de Groot PG. Antiphospholipid antibodies directed against a combination of phospholipids with prothrombin, protein C, or protein S: an explanation for their pathogenic mechanism? Blood. 1993. 81:2618–25.

16.Oosting JD., Derksen RH., Entjes HT., Bouma BN., de Groot PG. Lupus anticoagulant activity is frequently dependent on the presence of beta 2-glycoprotein I. Thromb Haemost. 1992. 67:499–502.

17.Roubey RA., Pratt CW., Buyon JP., Winfield JB. Lupus anticoagulant activity of autoimmune antiphospholipid antibodies is dependent upon beta 2-glycoprotein I. J Clin Invest. 1992. 90:1100–4.

18.Viard JP., Amoura Z., Bach JF. Association of anti-beta 2 glycoprotein I antibodies with lupus-type circulating anticoagulant and thrombosis in systemic lupus erythematosus. Am J Med. 1992. 93:181–6.

19.Chantarangkul V., Tripodi A., Arbini A., Mannucci PM. Silica clotting time (SCT) as a screening and confirmatory test for detection of the lupus anticoagulants. Thromb Res. 1992. 67:355–65.

20.Norbis F., Barbui T., Galli M. Diluted Russell's viper venom time and colloidal silica clotting time for the identification of the phospholipid-dependent inhibitors of coagulation. Thromb Res. 1997. 85:427–31.

21.Pengo V., Biasiolo A., Gresele P., Marongiu F., Erba N., Veschi F, et al. Survey of lupus anticoagulant diagnosis by central evaluation of positive plasma samples. J Thromb Haemost. 2007. 5:925–30.

22.Devreese KM. Evaluation of a new silica clotting time in the diagnosis of lupus anticoagulants. Thromb Res. 2007. 120:427–38.

23.Grypiotis P., Ruffatti A., Pengo V., Tonello M., Biasiolo A., Zamboni D, et al. Use of a new silica clotting time for diagnosing lupus anticoagulant in patients who meet the clinical criteria for antiphospho-lipid syndrome. J Clin Lab Anal. 2006. 20:15–8.

24.Brandt JT., Triplett DA., Alving B., Scharrer I. Criteria for the diagnosis of lupus anticoagulants: an update. On behalf of the Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the ISTH. Thromb Haemost. 1995. 74:1185–90.

25.Galli M., Ruggeri L., Barbui T. Differential effects of anti-beta2-glycoprotein I and antiprothrombin antibodies on the anticoagulant activity of activated protein C. Blood. 1998. 91:1999–2004.

26.de Laat B., Derksen RH., Urbanus RT., de Groot PG. IgG antibodies that recognize epitope Gly40-Arg43 in domain I of beta 2-glycoprotein I cause LAC, and their presence correlates strongly with thrombosis. Blood. 2005. 105:1540–5.